Date: Saturday, April 29, 2017
Session Time: 5:30pm-7:30pm
Presentation Time: 5:30pm-7:30pm
Location: Hall D1
Background: Allogeneic stem cell therapies aim to restore muscle tissue after traumatic loss or muscular dystrophies. Limited engraftment due to rejection is a major challenge. Muscle Derived Chimeric Cells (MDCC), created via ex vivo fusion of donor myoblast (MB) and recipient's mesenchymal stem cells (MSC), represent a promising therapeutic option. The aim of this study was to characterize human MDCC in vitro and to assess MDCC efficacy in engraftment and restoration of muscle function in Duchenne Muscular Dystrophy (DMD) mdx/scid mice model.
Methods: Fused MDCCs were cultured for 21 days to test cell proliferation, dystrophin expression (DE) and myogenic differentiation. Lymphocyte proliferation assay was performed to evaluate MDCC allogenicity: proliferation rate of responder T-cell (derived from same donors of MSC) was compared to responses after stimulation with media, 3rd party lymphocytes, and both MDCC parent cells. To test efficacy of human MDCCs in vivo, mdx/scid mice received intramuscular injections to gastrocnemius muscle (GM): Group 1 – vehicle (60mcl PBS), Group 2 – 0.25×106 of MSC and 0.25×106 MB without fusion, Group 3 – 0.5×106 of MB/MSC MDCC. Therapeutic effect was monitored by muscle function tests (grip strength, wire hanging, in situ muscle force). Assessment of GM weight, structure and DE was evaluated by histology and immunofluorescence at day 7 and 90 after MDCC delivery.
Results: Assessment of MDCC confirmed: parent cells genotype, dystrophin expression, proliferation and differentiation to mature skeletal myocytes. Proliferation of responder lymphocytes after stimulation with MDCC was 5.49% (SI=3.15), compared to positive controls of 55% (SI=31) after stimulation with 3rd party lymphocyte and 10% (SI=5.8) after stimulation with MB parent cells. MDCC survival and engraftment to GM was confirmed by DE of 16.18% at day 7 and 16.5% at 90 days and DE was co-localized with HLA-ABC expression. MDCC recipients showed 3-fold increase in muscle force (p=0.04) and improved fatigue tolerance compared to vehicle treated group.
Conclusions: This study confirmed efficacy of MDCC therapy in restoration of muscle function which correlated with dystrophin expression in the GM of mdx/scid mice. MDCC therapy represents a novel, universal approach for restoration of muscle function in muscular dystrophy, traumatic muscle tissue loss and for regeneration of muscle components of VCA.
CITATION INFORMATION: Siemionow M, Szilagyi E, Cwykiel J, Domaszewska-Szostek A, Heydemann A, Garcia-Martinez J. Transplantation of Chimeric Cells of Myoblast and Mesenchymal Stem Cell Origin for Restoration of Muscle Function. Am J Transplant. 2017;17 (suppl 3).
To cite this abstract in AMA style:Siemionow M, Szilagyi E, Cwykiel J, Domaszewska-Szostek A, Heydemann A, Garcia-Martinez J. Transplantation of Chimeric Cells of Myoblast and Mesenchymal Stem Cell Origin for Restoration of Muscle Function. [abstract]. Am J Transplant. 2017; 17 (suppl 3). https://atcmeetingabstracts.com/abstract/transplantation-of-chimeric-cells-of-myoblast-and-mesenchymal-stem-cell-origin-for-restoration-of-muscle-function/. Accessed September 29, 2020.
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